Functional Nanomaterials for Phototherapies of Cancer

We developed nanosized, reduced graphene oxide (nano-rGO) sheets with high near-infrared (NIR) light absorbance and biocompatibility for potential photothermal therapy. The single-layered nano-rGO sheets were ∼20 nm in average lateral dimension, functionalized noncovalently by amphiphilic PEGylated polymer chains to render stability in biological solutions and exhibited 6-fold higher NIR absorption than nonreduced, covalently PEGylated nano-GO. Attaching a targeting peptide bearing the Arg-Gly-Asp (RGD) motif to nano-rGO afforded selective cellular uptake in U87MG cancer cells and highly effective photoablation of cells in vitro. In the absence of any NIR irradiation, nano-rGO exhibited little toxicity in vitro at concentrations well above the doses needed for photothermal heating. This work established nano-rGO as a novel photothermal agent due to its small size, high photothermal efficiency, and low cost as compared to other NIR photothermal agents including gold nanomaterials and carbon nanotubes.

https://web.stanford.edu/group/dailab/Reprint/185.%20Ultrasmall%20Reduced%20Graphene%20Oxide%20with%20High%20Near-Infrared%20Absorbance%20for%20Photothermal%20Therapy.pdf

Ultrasmall Reduced Graphene Oxide with High Near-Infrared Absorbance for Photothermal Therapy

/pdf/nanoparticle-pegylation-for-imaging-and-therapy-45vkc0dds0.pdf

Nanoparticle PEGylation for imaging and therapy

Chemistries that Facilitate Nanotechnology Kim E. Sapsford,† W. Russ Algar, Lorenzo Berti, Kelly Boeneman Gemmill,‡ Brendan J. Casey,† Eunkeu Oh, Michael H. Stewart, and Igor L. Medintz*,‡ †Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States ‡Center for Bio/Molecular Science and Engineering Code 6900 and Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States Sotera Defense Solutions, Crofton, Maryland 21114, United States

Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology.

2.3. Ionic Liquids (ILs) 5374 2.4. Complexation Reactions on Oxidized CNTs 5375 2.5. Halogenation 5376 2.6. Cycloaddition Reactions 5377 2.7. Radical Additions 5379 2.8. Nucleophilic Additions 5381 2.9. Electrophilic Additions 5381 2.10. Electrochemical Modifications 5381 2.11. Plasma-Activation 5381 2.12. Mechanochemical Functionalizations 5382 3. Noncovalent Interactions 5382 3.1. Polynuclear Aromatic Compounds 5382 3.2. Interactions with Other Substances 5384 3.3. Interactions with Biomolecules 5385 4. Endohedral Filling 5386 4.1. Encapsulation of Fullerenes 5386 4.2. Encapsulation of Organic Substances 5387 4.3. Encapsulation of Inorganic Substances 5387 5. Decoration of CNTs with Metal Nanoparticles 5388 5.1. Covalent Linkage 5388 5.2. Direct Formation on Defect Sites 5388 5.3. Electroless Deposition 5388 5.4. Electrodeposition 5389 5.5. Chemical Decoration 5390 5.6. Deposition of Nanoparticles onto CNTs 5391 5.7. π-π Stacking and Electrostatic Interactions 5391 6. Concluding Remarks 5392 7. Acknowledgments 5392 8. References 5392

Current progress on the chemical modification of carbon nanotubes.

Nanomaterials have been actively pursued for biological and medical applications in recent years. Here, we report the synthesis of several new poly(ethylene glycol) grafted branched polymers for functionalization of various nanomaterials including carbon nanotubes, gold nanoparticles (NPs), and gold nanorods (NRs), affording high aqueous solubility and stability for these materials. We synthesize different surfactant polymers based upon poly(γ-glutamic acid) (γPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the abundant free carboxylic acid groups of γPGA for attaching lipophilic species such as pyrene or phospholipid, which bind to nanomaterials via robust physisorption. Additionally, the remaining carboxylic acids on γPGA or the amine-reactive anhydrides of PMHC18 are then PEGylated, providing extended hydrophilic groups, affording polymeric amphiphiles. We show that single-walled carbon nanotubes (SWNTs), Au NPs, and NRs functionalized by the polymers exhibit high stability in aqueous...

PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation

Nanomaterials have been actively pursued for biological and medical applications in recent years. Here, we report the synthesis of several new poly(ethylene glycol) grafted branched-polymers for functionalization of various nanomaterials including carbon nanotubes, gold nanoparticles (NP) and gold nanorods (NRs), affording high aqueous solubility and stability for these materials. We synthesize different surfactant polymers based upon poly-(g-glutamic acid) (gPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the abundant free carboxylic acid groups of gPGA for attaching lipophilic species such as pyrene or phospholipid, which bind to nanomaterials via robust physisorption. Additionally, the remaining carboxylic acids on gPGA or the amine-reactive anhydrides of PMHC18 are then PEGylated, providing extended hydrophilic groups, affording polymeric amphiphiles. We show that single-walled carbon nanotubes (SWNTs), Au NPs and NRs functionalized by the polymers exhibit high stability in aqueous solutions at different pHs, at elevated temperatures and in serum. Morever, the polymer-coated SWNTs exhibit remarkably long blood circulation (t1/2 22.1 h) upon intravenous injection into mice, far exceeding the previous record of 5.4 h. The ultra-long blood circulation time suggests greatly delayed clearance of nanomaterials by the reticuloendothelial system (RES) of mice, a highly desired property for in vivo applications of nanomaterials, including imaging and drug delivery.

/pdf/peg-branched-polymer-for-functionalization-of-nanomaterials-2o7y8o41yh.pdf

Nanomaterials hold much promise for biological applications, but they require appropriate functionalization to provide biocompatibility in biological environments. For non-covalent functionalization with biocompatible polymers, the polymer must also remain attached to the nanomaterial after removal of its excess to mimic the high dilution conditions of administration in vivo. Reported here are the synthesis and utilization singly-substituted conjugates of dextran and a phospholipid (Dextran-DSPE) as stable coatings for nanomaterials. Suspensions of single walled carbon nanotubes were found not only to be stable to phosphate buffered saline (PBS), serum, and a variety of pH’s after excess polymer removal, but also provide brighter photoluminescence than carbon nanotubes suspended by poly(ethylene glycol)-DSPE. In addition, both gold nanoparticles (AuNPs) and gold nanorods (AuNRs) were found to maintain their dispersion and characteristic optical absorbance after transfer into Dextran-DSPE, and were obtained in much better yield than similar suspensions with PEG-phospholipid and commonly used thiol-PEG. These suspensions were also stable to PBS, serum, and a variety of pH’s after removal of excess polymer. Dextran-DSPE thus shows great promise as a general surfactant material for the functionalization of a variety of nanomaterials, which could facilitate future biological applications.

/pdf/phospholipid-dextran-with-a-single-coupling-point-a-useful-296ov5bfof.pdf

Phospholipid-dextran with a single coupling point : a useful amphiphile for functionalization of nanomaterials

Nanomaterials hold much promise for biological applications, but they require appropriate functionalization to provide biocompatibility in biological environments. For non-covalent functionalization with biocompatible polymers, the polymer must also remain attached to the nanomaterial after removal of its excess to mimic the high dilution conditions of administration in vivo. Reported here are the synthesis and utilization singly-substituted conjugates of dextran and a phospholipid (Dextran-DSPE) as stable coatings for nanomaterials. Suspensions of single walled carbon nanotubes were found not only to be stable to phosphate buffered saline (PBS), serum, and a variety of pHs after excess polymer removal, but also provide brighter photoluminescence than carbon nanotubes suspended by poly(ethylene glycol)-DSPE. In addition, both gold nanoparticles (AuNPs) and gold nanorods (AuNRs) were found to maintain their dispersion and characteristic optical absorbance after transfer into Dextran-DSPE, and were obtained in much better yield than similar suspensions with PEG-phospholipid and commonly used thiol-PEG. These suspensions were also stable to PBS, serum, and a variety of pHs after removal of excess polymer. Dextran-DSPE thus shows great promise as a general surfactant material for the functionalization of a variety of nanomaterials, which could facilitate future biological applications.

/pdf/phospholipid-dextran-with-a-single-coupling-point-a-useful-2uxb1bzw0c.pdf

Giuseppe Prencipe

Papers

PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation

PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation

Phospholipid-dextran with a single coupling point : a useful amphiphile for functionalization of nanomaterials

Phospholipid-Dextran with a Single Coupling Point: a Useful Amphiphile for Functionalization of Nanomaterials